Hypoxia-associated alternative splicing signature in lung adenocarcinoma

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References

• 1. Siegel RL, Miller KD, Jemal A. Cancer statistics, 2019. CA Cancer J. Clin. 69(1), 7–34 (2019).
  MedlineGoogle Scholar
• 2. Chen Z, Fillmore CM, Hammerman PS, Kim CF, Wong K-K. Non-small-cell lung cancers: a heterogeneous set of diseases. Nat. Rev. Cancer 14(8), 535–546 (2014).
  Medline CASGoogle Scholar
• 3. Bray F, Ferlay J, Soerjomataram I, Siegel RL, Torre LA, Jemal A. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J. Clin. 68(6), 394–424 (2018).
  MedlineGoogle Scholar
• 4. Miller KD, Nogueira L, Mariotto AB et al. Cancer treatment and survivorship statistics, 2019. CA Cancer J. Clin. 69(5), 363–385 (2019).
  MedlineGoogle Scholar
• 5. Gray EP, Teare MD, Stevens J, Archer R. Risk prediction models for lung cancer: a systematic review. Clin. Lung Cancer 17(2), 95–106 (2016).
  MedlineGoogle Scholar
• 6. Mckeown SR. Defining normoxia, physoxia and hypoxia in tumours – implications for treatment response. Br. J. Radiol. 87(1035), 20130676 (2014).
  Medline CASGoogle Scholar
• 7. Bharti SK, Kakkad S, Danhier P et al. Hypoxia patterns in primary and metastatic prostate cancer environments. Neoplasia 21(2), 239–246 (2019).
  Medline CASGoogle Scholar
• 8. Chiu DK, Tse AP, Xu IM et al. Hypoxia inducible factor HIF-1 promotes myeloid-derived suppressor cells accumulation through ENTPD2/CD39L1 in hepatocellular carcinoma. Nat. Commun. 8(1), 517 (2017). •• Reported hypoxia as a cause of myeloid-derived suppressor cell accumulation, which allow cancers to escape immune surveillance and become nonresponsive to immune checkpoint blockade.
  MedlineGoogle Scholar
• 9. Salem A, Asselin MC, Reymen B et al. Targeting hypoxia to improve non-small-cell lung cancer outcome. J. Natl Cancer Inst. 110(1) doi:10.1093/jnci/djx160 (2018).
  MedlineGoogle Scholar
• 10. Wang Y, Shang W, Niu M, Tian J, Xu K. Hypoxia-active nanoparticles used in tumor theranostic. Int. J. Nanomed. 14, 3705–3722 (2019).
  Medline CASGoogle Scholar
• 11. Climente-González H, Porta-Pardo E, Godzik A, Eyras E. The functional impact of alternative splicing in cancer. Cell Rep. 20(9), 2215–2226 (2017). •• Revealed that a subset of alternative splicing changes affect protein domain families that are frequently mutated in tumors and potentially disrupt protein–protein interactions in cancer-related pathways.
  Medline CASGoogle Scholar
• 12. Jing X, Yang F, Shao C et al. Role of hypoxia in cancer therapy by regulating the tumor microenvironment. Mol. Cancer 18(1), 157 (2019).
  MedlineGoogle Scholar
• 13. Yang Y, Qu A, Wu Q et al. Prognostic value of a hypoxia-related microRNA signature in patients with colorectal cancer. Aging 12(1), 35–52 (2020).
  Medline CASGoogle Scholar
• 14. Liu Y, Wu J, Huang W et al. Development and validation of a hypoxia-immune-based microenvironment gene signature for risk stratification in gastric cancer. J. Transl. Med. 18(1), 201 (2020).
  Medline CASGoogle Scholar
• 15. Zhang B, Tang B, Gao J, Li J, Kong L, Qin L. A hypoxia-related signature for clinically predicting diagnosis, prognosis and immune microenvironment of hepatocellular carcinoma patients. J. Transl. Med. 18(1), 342 (2020).
  Medline CASGoogle Scholar
• 16. Farina AR, Cappabianca L, Sebastiano M, Zelli V, Guadagni S, Mackay AR. Hypoxia-induced alternative splicing: the 11th hallmark of cancer. J. Exp. Clin. Cancer Res. 39(1), 110 (2020).
  MedlineGoogle Scholar
• 17. Bowler E, Porazinski S, Uzor S et al. Hypoxia leads to significant changes in alternative splicing and elevated expression of CLK splice factor kinases in PC3 prostate cancer cells. BMC Cancer 18(1), 355 (2018).
  MedlineGoogle Scholar
• 18. Hirschfeld M, Zur Hausen A, Bettendorf H, Jäger M, Stickeler E. Alternative splicing of Cyr61 is regulated by hypoxia and significantly changed in breast cancer. Cancer Res. 69(5), 2082–2090 (2009).
  Medline CASGoogle Scholar
• 19. Pan Q, Shai O, Lee LJ, Frey BJ, Blencowe BJ. Deep surveying of alternative splicing complexity in the human transcriptome by high-throughput sequencing. Nat. Genet. 40(12), 1413–1415 (2008).
  Medline CASGoogle Scholar
• 20. Lee SC, Abdel-Wahab O. Therapeutic targeting of splicing in cancer. Nat. Med. 22(9), 976–986 (2016). •• Presented strategies that exist and are in development to target altered dependency on the spliceosome as well as aberrant splicing in cancer.
  Medline CASGoogle Scholar
• 21. Marzese DM, Manughian-Peter AO, Orozco JIJ, Hoon DSB. Alternative splicing and cancer metastasis: prognostic and therapeutic applications. Clin. Exp. Metastasis 35(5), 393–402 (2018).
  Medline CASGoogle Scholar
• 22. Wu F, Chen Q, Liu C et al. Profiles of prognostic alternative splicing signature in hepatocellular carcinoma. Cancer Med. 9(6), 2171–2180 (2020).
  Medline CASGoogle Scholar
• 23. Mao S, Li Y, Lu Z et al. Survival-associated alternative splicing signatures in esophageal carcinoma. Carcinogenesis 40(1), 121–130 (2019).
  Medline CASGoogle Scholar
• 24. Song J, Liu YD, Su J, Yuan D, Sun F, Zhu J. Systematic analysis of alternative splicing signature unveils prognostic predictor for kidney renal clear cell carcinoma. J. Cell. Physiol. 234(12), 22753–22764 (2019).
  Medline CASGoogle Scholar
• 25. Huang R, Liao X, Li Q. Identification and validation of potential prognostic gene biomarkers for predicting survival in patients with acute myeloid leukemia. Onco Targets Ther. 10, 5243–5254 (2017).
  MedlineGoogle Scholar
• 26. Wang N, Guo H, Dong Z et al. Establishment and validation of a 7-microRNA prognostic signature for non-small cell lung cancer. Cancer Manag. Res. 10, 3463–3471 (2018).
  Medline CASGoogle Scholar
• 27. Jiang W, Guo Q, Wang C, Zhu Y. A nomogram based on 9-lncRNAs signature for improving prognostic prediction of clear cell renal cell carcinoma. Cancer Cell Int. 19, 208 (2019).
  MedlineGoogle Scholar
• 28. Piva F, Giulietti M, Burini AB, Principato G. SpliceAid 2: a database of human splicing factors expression data and RNA target motifs. Hum. Mutat. 33(1), 81–85 (2012).
  Medline CASGoogle Scholar
• 29. Zhang W, Shen Y, Feng G. Predicting the survival of patients with lung adenocarcinoma using a four-gene prognosis risk model. Oncology Lett. 18(1), 535–544 (2019).
  Medline CASGoogle Scholar
• 30. Wei W, Lv Y, Gan Z, Zhang Y, Han X, Xu Z. Identification of key genes involved in the metastasis of clear cell renal cell carcinoma. Oncology Lett. 17(5), 4321–4328 (2019).
  Medline CASGoogle Scholar
• 31. Chakraborty H, Hossain A. R package to estimate intracluster correlation coefficient with confidence interval for binary data. Comput. Methods Programs Biomed. 155, 85–92 (2018).
  MedlineGoogle Scholar
• 32. Foroutan M, Bhuva DD, Lyu R, Horan K, Cursons J, Davis MJ. Single sample scoring of molecular phenotypes. BMC Bioinformatics 19(1), 404 (2018).
  Medline CASGoogle Scholar
• 33. Li H, Tong L, Tao H, Liu Z. Genome-wide analysis of the hypoxia-related DNA methylation-driven genes in lung adenocarcinoma progression. Biosci. Rep. 40(2), BSR20194200 (2020).
  Medline CASGoogle Scholar
• 34. Mayakonda A, Lin DC, Assenov Y, Plass C, Koeffler HP. Maftools: efficient and comprehensive analysis of somatic variants in cancer. Genome Res. 28(11), 1747–1756 (2018).
  Medline CASGoogle Scholar
• 35. Yarchoan M, Hopkins A, Jaffee EM. Tumor mutational burden and response rate to PD-1 inhibition. N. Engl. J. Med. 377(25), 2500–2501 (2017).
  MedlineGoogle Scholar
• 36. Samstein RM, Lee CH, Shoushtari AN et al. Tumor mutational load predicts survival after immunotherapy across multiple cancer types. Nat. Genet. 51(2), 202–206 (2019).
  Medline CASGoogle Scholar
• 37. Schrock AB, Ouyang C, Sandhu J et al. Tumor mutational burden is predictive of response to immune checkpoint inhibitors in MSI-high metastatic colorectal cancer. Ann. Oncol. 30(7), 1096–1103 (2019).
  Medline CASGoogle Scholar
• 38. Carter BW, Lichtenberger JP 3rd, Benveniste MK et al. Revisions to the TNM staging of lung cancer: rationale, significance, and clinical application. Radiographics 38(2), 374–391 (2018).
  MedlineGoogle Scholar
• 39. De Sousa VML, Carvalho L. Heterogeneity in lung cancer. Pathobiology 85(1-2), 96–107 (2018).
  MedlineGoogle Scholar
• 40. Dawood S, Austin L, Cristofanilli M. Cancer stem cells: implications for cancer therapy. Oncology 28(12), 1101–1107 (2014).
  MedlineGoogle Scholar
• 41. Hua X, Zhao W, Pesatori AC et al. Genetic and epigenetic intratumor heterogeneity impacts prognosis of lung adenocarcinoma. Nat. Commun. 11(1), 2459 (2020).
  Medline CASGoogle Scholar
• 42. Lim W, Ridge CA, Nicholson AG, Mirsadraee S. The 8th lung cancer TNM classification and clinical staging system: review of the changes and clinical implications. Quant. Imaging Med. Surg. 8(7), 709–718 (2018).
  MedlineGoogle Scholar
• 43. Zhong J, Ren X, Chen Z et al. miR-21-5p promotes lung adenocarcinoma progression partially through targeting SET/TAF-Iα. Life Sci. 231, 116539 (2019).
  Medline CASGoogle Scholar
• 44. Dong HX, Wang R, Jin XY, Zeng J, Pan J. LncRNA DGCR5 promotes lung adenocarcinoma (LUAD) progression via inhibiting hsa-mir-22-3p. J. Cell. Physiol. 233(5), 4126–4136 (2018).
  Medline CASGoogle Scholar
• 45. Lu QC, Rui ZH, Guo ZL, Xie W, Shan S, Ren T. LncRNA-DANCR contributes to lung adenocarcinoma progression by sponging miR-496 to modulate mTOR expression. J. Cell. Mol. Med. 22(3), 1527–1537 (2018).
  Medline CASGoogle Scholar
• 46. Qiu M, Xia W, Chen R et al. The circular RNA circPRKCI promotes tumor growth in lung adenocarcinoma. Cancer Res. 78(11), 2839–2851 (2018).
  Medline CASGoogle Scholar
• 47. Zhang HM, Yang B, Chen HF et al. Prognosis-related miRNA bioinformatics screening of lung adenocarcinoma and its clinical significance. Chin. J. Appl. Physiol. 34(6), 530–535 (2018).
  CASGoogle Scholar
• 48. Liang Y, Song J, He D et al. Systematic analysis of survival-associated alternative splicing signatures uncovers prognostic predictors for head and neck cancer. J. Cell. Physiol. 234(9), 15836–15846 (2019).
  CASGoogle Scholar
• 49. Wu HY, Peng ZG, He RQ et al. Prognostic index of aberrant mRNA splicing profiling acts as a predictive indicator for hepatocellular carcinoma based on TCGA SpliceSeq data. Int. J. Oncol. 55(2), 425–438 (2019).
  Medline CASGoogle Scholar
• 50. Kanopka A. Cell survival: interplay between hypoxia and pre-mRNA splicing. Exp. Cell Res. 356(2), 187–191 (2017).
  Medline CASGoogle Scholar
• 51. Bates DO, Cui TG, Doughty JM et al. VEGF165b, an inhibitory splice variant of vascular endothelial growth factor, is down-regulated in renal cell carcinoma. Cancer Res. 62(14), 4123–4131 (2002).
  Medline CASGoogle Scholar
• 52. Makino Y, Kanopka A, Wilson WJ, Tanaka H, Poellinger L. Inhibitory PAS domain protein (IPAS) is a hypoxia-inducible splicing variant of the hypoxia-inducible factor-3alpha locus. J. Biol. Chem. 277(36), 32405–32408 (2002).
  Medline CASGoogle Scholar
• 53. Peciuliene I, Vilys L, Jakubauskiene E, Zaliauskiene L, Kanopka A. Hypoxia alters splicing of the cancer associated Fas gene. Exp. Cell Res. 380(1), 29–35 (2019). • First report that antiapoptotic Fas mRNA isoform formation is regulated by cellular microenvironment hypoxia.
  Medline CASGoogle Scholar
• 54. Nakayama K, Kataoka N. Regulation of gene expression under hypoxic conditions. Int. J. Mol. Sci. 20(13), 3278 (2019). • Presented RNA splicing regulations under hypoxic conditions, which are mediated by splicing factors and their kinases.
  CASGoogle Scholar
• 55. Wang Y, Piao J, Wang Q et al. Paip1 predicts poor prognosis and promotes tumor progression through AKT/GSK-3β pathway in lung adenocarcinoma. Hum. Pathol. 86, 233–242 (2019).
  Medline CASGoogle Scholar
• 56. Fernandez P, Carretero J, Medina PP et al. Distinctive gene expression of human lung adenocarcinomas carrying LKB1 mutations. Oncogene 23(29), 5084–5091 (2004).
  Medline CASGoogle Scholar
• 57. Huang H, Li T, Chen M et al. Identification and validation of NOLC1 as a potential target for enhancing sensitivity in multidrug resistant non-small-cell lung cancer cells. Cell. Mol. Biol. Lett. 23, 54 (2018).
  Medline CASGoogle Scholar
• 58. Zheng P, Li L. FANCI cooperates with IMPDH2 to promote lung adenocarcinoma tumor growth via a MEK/ERK/MMPs pathway. Onco Targets Ther. 13, 451–463 (2020).
  Medline CASGoogle Scholar
• 59. Li J, Liu L, Liu X, Xu P, Hu Q, Yu Y. The role of upregulated DDX11 as a potential prognostic and diagnostic biomarker in lung adenocarcinoma. J. Cancer 10(18), 4208–4216 (2019).
  Medline CASGoogle Scholar
• 60. Wu K, Hu M, Chen Z et al. Asiatic acid enhances survival of human AC16 cardiomyocytes under hypoxia by upregulating miR-1290. IUBMB Life 69(9), 660–667 (2017).
  Medline CASGoogle Scholar
• 61. Bonkowsky JL, Son JH. Hypoxia and connectivity in the developing vertebrate nervous system. Dis. Model. Mech. 11(12), dmm037127 (2018).
  Medline CASGoogle Scholar
• 62. Xu Z, Lv H, Wang Y et al. HAND2-AS1 inhibits gastric adenocarcinoma cells proliferation and aerobic glycolysis via miRNAs sponge. Cancer Manag. Res. 1(12), 3053–3068 (2020).
  Google Scholar
• 63. Jyotsana N, Heuser M. Exploiting differential RNA splicing patterns: a potential new group of therapeutic targets in cancer. Expert Opin. Ther. Targets 22(2), 107–121 (2018). •• Targeting aberrant splicing is an early but emerging field in cancer treatment.
  Medline CASGoogle Scholar
• 64. Bonomi S, Gallo S, Catillo M, Pignataro D, Biamonti G, Ghigna C. Oncogenic alternative splicing switches: role in cancer progression and prospects for therapy. Int. J. Cell Biol. 2013, 962038 (2013).
  MedlineGoogle Scholar
• 65. Fan J, Wang K, Du X et al. ALYREF links 3′-end processing to nuclear export of non-polyadenylated mRNAs. EMBO J. 38(9), 2019).
  Google Scholar
• 66. Shi M, Zhang H, Wu X et al. ALYREF mainly binds to the 5′ and the 3′ regions of the mRNA in vivo. Nucleic Acids Res. 45(16), 9640–9653 (2017).
  Medline CASGoogle Scholar
• 67. Ouyang D, Yang P, Cai J, Sun S, Wang Z. Comprehensive analysis of prognostic alternative splicing signature in cervical cancer. Cancer Cell Int. 20, 221 (2020).
  Medline CASGoogle Scholar
• 68. Dou N, Yang D, Yu S, Wu B, Gao Y, Li Y. SNRPA enhances tumour cell growth in gastric cancer through modulating NGF expression. Cell Prolif. 51(5), e12484 (2018).
  MedlineGoogle Scholar
• 69. Quidville V, Alsafadi S, Goubar A et al. Targeting the deregulated spliceosome core machinery in cancer cells triggers mTOR blockade and autophagy. Cancer Res. 73(7), 2247–2258 (2013).
  Medline CASGoogle Scholar
• 70. Sun C, Wang G, Wrighton KH et al. Regulation of p27(Kip1) phosphorylation and G1 cell cycle progression by protein phosphatase PPM1G. Am. J. Cancer Res. 6(10), 2207–2220 (2016).
  Medline CASGoogle Scholar
• 71. Yi M, Li T, Qin S et al. Identifying tumorigenesis and prognosis-related genes of lung adenocarcinoma: based on weighted gene coexpression network analysis. Biomed. Res. Int. 2020, 4169691 (2020).
  MedlineGoogle Scholar
• 72. Liu J, Stevens PD, Eshleman NE, Gao T. Protein phosphatase PPM1G regulates protein translation and cell growth by dephosphorylating 4E binding protein 1 (4E-BP1). J. Biol. Chem. 288(32), 23225–23233 (2013).
  Medline CASGoogle Scholar
• 73. Kim YD, Lee J, Kim HS et al. The unique spliceosome signature of human pluripotent stem cells is mediated by SNRPA1, SNRPD1, and PNN. Stem Cell Res. 22, 43–53 (2017).
  Medline CASGoogle Scholar
• 74. Luo C, Lei M, Zhang Y et al. Systematic construction and validation of an immune prognostic model for lung adenocarcinoma. J. Cell. Mol. Med. 24(2), 1233–1244 (2020).
  Medline CASGoogle Scholar
• 75. Noman MZ, Hasmim M, Messai Y et al. Hypoxia: a key player in antitumor immune response. A review in the theme: cellular responses to hypoxia.. Am. J. Physiol. Cell Physiol. 309(9),C569–C579 (2015).
  Google Scholar
• 76. Wynants L, Van Calster B, Collins GS et al. Prediction models for diagnosis and prognosis of COVID-19 infection: systematic review and critical appraisal. BMJ 369(7), m1328 (2020).
  MedlineGoogle Scholar